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1.
Nature ; 600(7887): 59-63, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34666339

RESUMO

Mare volcanics on the Moon are the key record of thermo-chemical evolution throughout most of lunar history1-3. Young mare basalts-mainly distributed in a region rich in potassium, rare-earth elements and phosphorus (KREEP) in Oceanus Procellarum, called the Procellarum KREEP Terrane (PKT)4-were thought to be formed from KREEP-rich sources at depth5-7. However, this hypothesis has not been tested with young basalts from the PKT. Here we present a petrological and geochemical study of the basalt clasts from the PKT returned by the Chang'e-5 mission8. These two-billion-year-old basalts are the youngest lunar samples reported so far9. Bulk rock compositions have moderate titanium and high iron contents  with KREEP-like rare-earth-element and high thorium concentrations. However, strontium-neodymium isotopes indicate that these basalts were derived from a non-KREEP mantle source. To produce the high abundances of rare-earth elements and thorium, low-degree partial melting and extensive fractional crystallization are required. Our results indicate that the KREEP association may not be a prerequisite for young mare volcanism. Absolving the need to invoke heat-producing elements in their source implies a more sustained cooling history of the lunar interior to generate the Moon's youngest melts.

2.
Blood ; 139(11): 1670-1683, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-34871371

RESUMO

Pediatric and young adult (YA) patients with acute myeloid leukemia (AML) who relapse after allogeneic hematopoietic cell transplantation (HCT) have an extremely poor prognosis. Standard salvage chemotherapy and donor lymphocyte infusions (DLIs) have little curative potential. Previous studies showed that natural killer (NK) cells can be stimulated ex vivo with interleukin-12 (IL-12), -15, and -18 to generate memory-like (ML) NK cells with enhanced antileukemia responses. We treated 9 pediatric/YA patients with post-HCT relapsed AML with donor ML NK cells in a phase 1 trial. Patients received fludarabine, cytarabine, and filgrastim followed 2 weeks later by infusion of donor lymphocytes and ML NK cells from the original HCT donor. ML NK cells were successfully generated from haploidentical and matched-related and -unrelated donors. After infusion, donor-derived ML NK cells expanded and maintained an ML multidimensional mass cytometry phenotype for >3 months. Furthermore, ML NK cells exhibited persistent functional responses as evidenced by leukemia-triggered interferon-γ production. After DLI and ML NK cell adoptive transfer, 4 of 8 evaluable patients achieved complete remission at day 28. Two patients maintained a durable remission for >3 months, with 1 patient in remission for >2 years. No significant toxicity was experienced. This study demonstrates that, in a compatible post-HCT immune environment, donor ML NK cells robustly expand and persist with potent antileukemic activity in the absence of exogenous cytokines. ML NK cells in combination with DLI present a novel immunotherapy platform for AML that has relapsed after allogeneic HCT. This trial was registered at https://clinicaltrials.gov as #NCT03068819.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Criança , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Células Matadoras Naturais , Leucemia Mieloide Aguda/terapia , Transplante Homólogo , Doadores não Relacionados
3.
Lupus ; 32(2): 252-262, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36508734

RESUMO

BACKGROUND: Lupus nephritis (LN) is a major and severe organ involvement in systemic lupus erythematosus (SLE), whose diagnosis and treatment necessitate to perform kidney biopsy, which is an invasive procedure. Non-invasive urine biomarkers are an active area of investigation to support LN diagnosis and management. OBJECTIVE: To investigate the role of urinary galectin-3 binding protein (u-Gal-3BP) as a candidate biomarker of renal disease in biopsy proven LN. PATIENTS AND METHODS: Levels of u-Gal-3BP were investigated in a cross-sectional fashion by ELISA in 270 subjects: 86 LN patients, 63 active SLE patients with no kidney involvement, 73 SLE patients with inactive disease and 48 age and sex-matched population-based controls (PBC). Moreover, urine samples were analysed separately by ELISA for additional markers of kidney pathology: neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule-1 (KIM-1) and galectin-3 (Gal-3). The concentrations of all studied molecules were normalized to urine creatinine levels. In 10 patients, post-treatment levels of the biomarkers were measured. RESULTS: Normalized u-Gal-3BP levels were higher in LN patients compared to the other groups (p < .0001). Comparing different LN classes, u-Gal-3BP levels were higher among patients with proliferative (class III/IV) and membranous (class V) as compared to mesangial (class II) forms (p = .04). In proliferative forms, u-Gal-3BP levels correlated with the activity index in renal biopsies (r = 0.42, p = .004). Moreover, in a subset of 10 patients with repeated kidney biopsy and urine sampling before and after induction treatment, a significant decrease of u-Gal-3BP was observed (p = .03). Among the other markers, KIM-1 was also able to discriminate LN from the other groups, while NGAL, OPN and Gal-3 could not in this cohort. CONCLUSION: Given its ability to discriminate LN patients from active non-renal and inactive SLE patients, the observed correlation with the activity index in renal biopsies, and its levels declining following treatment, u-Gal-3BP shows promise as a non-invasive urinary biomarker to help detecting and to monitor renal involvement in SLE patients and should be validated in larger cohorts.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Biomarcadores/urina , Estudos Transversais , Galectina 3/metabolismo , Lipocalina-2/urina , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/patologia
4.
Sensors (Basel) ; 23(13)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37447928

RESUMO

This paper presents an RGB-NIR (Near Infrared) dual-modality technique to analyze the remote photoplethysmogram (rPPG) signal and hence estimate the heart rate (in beats per minute), from a facial image sequence. Our main innovative contribution is the introduction of several denoising techniques such as Modified Amplitude Selective Filtering (MASF), Wavelet Decomposition (WD), and Robust Principal Component Analysis (RPCA), which take advantage of RGB and NIR band characteristics to uncover the rPPG signals effectively through this Independent Component Analysis (ICA)-based algorithm. Two datasets, of which one is the public PURE dataset and the other is the CCUHR dataset built with a popular Intel RealSense D435 RGB-D camera, are adopted in our experiments. Facial video sequences in the two datasets are diverse in nature with normal brightness, under-illumination (i.e., dark), and facial motion. Experimental results show that the proposed method has reached competitive accuracies among the state-of-the-art methods even at a shorter video length. For example, our method achieves MAE = 4.45 bpm (beats per minute) and RMSE = 6.18 bpm for RGB-NIR videos of 10 and 20 s in the CCUHR dataset and MAE = 3.24 bpm and RMSE = 4.1 bpm for RGB videos of 60-s in the PURE dataset. Our system has the advantages of accessible and affordable hardware, simple and fast computations, and wide realistic applications.


Assuntos
Algoritmos , Face , Frequência Cardíaca/fisiologia , Movimento (Física) , Iluminação , Fotopletismografia/métodos , Processamento de Sinais Assistido por Computador
5.
J Pathol ; 252(2): 101-113, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32617978

RESUMO

The histone demethylase KDM4B functions as a key co-activator for the androgen receptor (AR) and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 methylation marks. Constitutively active androgen receptor confers anti-androgen resistance in advanced prostate cancer. However, the role of KDM4B in resistance to next-generation anti-androgens and the mechanisms of KDM4B regulation are poorly defined. Here we found that KDM4B is overexpressed in enzalutamide-resistant prostate cancer cells. Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next-generation AR-targeted therapy. Inhibition of KDM4B significantly inhibited prostate tumor cell growth in xenografts, and improved enzalutamide treatments through suppression of c-Myc. Clinically, KDM4B expression was found upregulated and to correlate with prostate cancer progression and poor prognosis. Our results revealed a novel mechanism of anti-androgen resistance via histone demethylase alteration which could be targeted through inhibition of KDM4B to reduce AR-dependent c-Myc expression and overcome resistance to AR-targeted therapies. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Adenocarcinoma/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Adenocarcinoma/patologia , Antagonistas de Receptores de Andrógenos/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias de Próstata Resistentes à Castração/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo
6.
Arch Toxicol ; 95(2): 489-508, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33236189

RESUMO

5F-MDMB-PINACA and 4F-MDMB-BINACA are synthetic cannabinoids (SCs) that elicit cannabinoid psychoactive effects. Defining pharmacokinetic-pharmacodynamic (PK-PD) relationships governing SCs and their metabolites are paramount to investigating their in vivo toxicological outcomes. However, the disposition kinetics and cannabinoid receptor (CB) activities of the primary metabolites of SCs are largely unknown. Additionally, reasons underlying the selection of ester hydrolysis metabolites (EHMs) as urinary biomarkers are often unclear. Here, metabolic reaction phenotyping was performed to identify key metabolizing enzymes of the parent SCs. Hepatic clearances of parent SCs and their EHMs were estimated from microsomal metabolic stability studies. Renal clearances were simulated using a mechanistic kidney model incorporating in vitro permeability and organic anionic transporter 3 (OAT3)-mediated uptake data. Overall clearances were considered in tandem with estimated volumes of distribution for in vivo biological half-lives (t1/2) predictions. Interactions of the compounds with CB1 and CB2 were investigated using a G-protein coupled receptor activation assay. We demonstrated that similar enzymatic isoforms were implicated in the metabolism of 5F-MDMB-PINACA and 4F-MDMB-BINACA. Our in vivo t1/2 determinations verified the rapid elimination of parent SCs and suggest prolonged circulation of their EHMs. The pronounced attenuation of the potencies and efficacies of the metabolites against CB1 and CB2 further suggests how toxic manifestations of SC abuse are likely precipitated by augmented exposure to parent SCs. Notably, basolateral OAT3-mediated uptake of the EHMs substantiates their higher urinary abundance. These novel insights underscore the importance of mechanistic, quantitative and systematic characterization of PK-PD relationships in rationalizing the toxicities of SCs.


Assuntos
Canabinoides/farmacocinética , Canabinoides/toxicidade , Ésteres/metabolismo , Animais , Biomarcadores/metabolismo , Cães , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Células HEK293 , Humanos , Hidrólise , Células Madin Darby de Rim Canino , Masculino , Microssomos Hepáticos/metabolismo , Urina/química
7.
Proc Natl Acad Sci U S A ; 115(35): 8682-8687, 2018 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-30104354

RESUMO

The extreme Sr, Nd, Hf, and Pb isotopic compositions found in Pitcairn Island basalts have been labeled enriched mantle 1 (EM1), characterizing them as one of the isotopic mantle end members. The EM1 origin has been vigorously debated for over 25 years, with interpretations ranging from delaminated subcontinental lithosphere, to recycled lower continental crust, to recycled oceanic crust carrying ancient pelagic sediments, all of which may potentially generate the requisite radiogenic isotopic composition. Here we find that δ26Mg ratios in Pitcairn EM1 basalts are significantly lower than in normal mantle and are the lowest values so far recorded in oceanic basalts. A global survey of Mg isotopic compositions of potentially recycled components shows that marine carbonates constitute the most common and typical reservoir invariably characterized by extremely low δ26Mg values. We therefore infer that the subnormal δ26Mg of the Pitcairn EM1 component originates from subducted marine carbonates. This, combined with previously published evidence showing exceptionally unradiogenic Pb as well as sulfur isotopes affected by mass-independent fractionation, suggests that the Pitcairn EM1 component is most likely derived from late Archean subducted carbonate-bearing sediments. However, the low Ca/Al ratios of Pitcairn lavas are inconsistent with experimental evidence showing high Ca/Al ratios in melts derived from carbonate-bearing mantle sources. We suggest that carbonate-silicate reactions in the late Archean subducted sediments exhausted the carbonates, but the isotopically light magnesium of the carbonate was incorporated in the silicates, which then entered the lower mantle and ultimately became the Pitcairn plume source.

8.
Carcinogenesis ; 41(1): 56-66, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-31046116

RESUMO

The forkhead box A1 (FOXA1), one of the forkhead class of DNA-binding proteins, functions as a transcription factor and plays a vital role in cellular control of embryonic development and cancer progression. Downregulation of FOXA1 has reported in several types of cancer, which contributes to cancer cell survival and chemoresistance. However, the mechanism for FOXA1 downregulation in cancer remains unclear. Here, we report that the ubiquitination enzyme zinc finger protein 91 (ZFP91) ubiquitinates and destabilizes FOXA1, which promotes cancer cell growth. High level of ZFP91 expression correlates with low level of FOXA1 protein in human gastric cancer (GC) cell lines and patient samples. Furthermore, ZFP91 knockdown reduces FOXA1 polyubiquitination, which decreases FOXA1 turnover and enhances cellular sensitivity to chemotherapy. Taken together, our findings reveal ZFP91-FOXA1 axis plays an important role in promoting GC progression and provides us a potential therapeutic intervention in the treatment of GC.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Neoplasias Gástricas/genética , Ubiquitina-Proteína Ligases/metabolismo , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Regulação para Baixo , Feminino , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Estabilidade Proteica , Proteólise , RNA Interferente Pequeno/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Ubiquitina-Proteína Ligases/genética , Ubiquitinação/genética , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Phys Rev Lett ; 125(22): 222301, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33315427

RESUMO

Particle production in ultrarelativistic heavy ion collisions depends on the details of the nucleon density distributions in the colliding nuclei. We demonstrate that the charged hadron multiplicity distributions in isobaric collisions at ultrarelativistic energies provide a novel approach to determine the poorly known neutron density distributions and thus the neutron skin thickness in finite nuclei, which can in turn put stringent constraints on the nuclear symmetry energy.

10.
Cancer Sci ; 110(10): 3145-3156, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31393050

RESUMO

Yes-associated protein (YAP) is a component of the canonical Hippo signaling pathway that is known to play essential roles in modulating organ size, development, and tumorigenesis. Activation or upregulation of YAP1, which contributes to cancer cell survival and chemoresistance, has been verified in different types of human cancers. However, the molecular mechanism of YAP1 upregulation in cancer is still unclear. Here we report that the E3 ubiquitin ligase STUB1 ubiquitinates and destabilizes YAP1, thereby inhibiting cancer cell survival. Low levels of STUB1 expression were correlated with increased protein levels of YAP1 in human gastric cancer cell lines and patient samples. Moreover, we revealed that STUB1 ubiquitinates YAP1 at the K280 site by K48-linked polyubiquitination, which in turn increases YAP1 turnover and promotes cellular chemosensitivity. Overall, our study establishes YAP1 ubiquitination and degradation mediated by the E3 ligase STUB1 as an important regulatory mechanism in gastric cancer, and provides a rationale for potential therapeutic interventions.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Neoplasias Gástricas/patologia , Ubiquitina-Proteína Ligases/metabolismo , Animais , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Lisina/metabolismo , Camundongos , Transplante de Neoplasias , Estabilidade Proteica , Proteólise , Transdução de Sinais , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Fatores de Transcrição , Ubiquitinação , Proteínas de Sinalização YAP
11.
Ann Surg Oncol ; 23(2): 619-25, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26474558

RESUMO

BACKGROUND: Thymic carcinoma is a type of rare and highly malignant tumor that originates from the thymic epithelium. Treatment and prognosis of thymic carcinoma remain controversial. We retrospectively analyzed survival data from a large-sample multicenter database in China. METHODS: The Chinese Alliance for Research of Thymoma constructed a retrospective database of patients with thymic epithelial tumors, which enrolled 1930 patients from January 1996 to August 2013, including 329 with thymic carcinomas. In this study, we analyzed clinical, pathologic, and treatment information, measured long-term survival rates, and identified relevant prognostic factors. RESULTS: Of 329 patients, R0 resection was performed in 211 (57.7 %), R1 in 34 (9.2 %), and R2 in 84 (22.5 %).The 3-, 5-, and 10-year survival rates were 78.3, 67.1, and 47.9 %, respectively. In univariate analysis, early Masaoka-Koga stage, R0 resection, and postoperative radiotherapy were associated with better overall survival.Early Masaoka-Koga stage and postoperative radiotherapy were also associated with disease-free survival. In multivariate analyses, R0 resection, Masaoka-Koga stage, and postoperative radiotherapy were significant prognostic factors of survival. CONCLUSIONS: Complete resection is the preferred primary treatment for thymic carcinoma. R0 resection, early Masaoka-Koga stage, and postoperative radiotherapy are significant predictors of improved survival.


Assuntos
Carcinoma Neuroendócrino/mortalidade , Carcinoma de Células Escamosas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Timectomia/mortalidade , Timoma/mortalidade , Neoplasias do Timo/mortalidade , Adulto , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Timoma/patologia , Timoma/cirurgia , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia
12.
J Immunol ; 188(12): 5839-49, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22573808

RESUMO

Upon Ag exposure, most memory T cells undergo restimulation-induced cell death. In this article, we describe a novel synthetic agonist, an N-terminal extended decamer peptide expressed as a single-chain trimer, the amino-terminal extended peptide MHC class I single-chain trimer (AT-SCT), which preferentially promotes the growth of memory human CD8(+) T cells with minimal restimulation-induced cell death. Using CMV pp65 and melanoma gp100 Ags, we observe the in vitro numerical expansion of a clonally diverse polyfunctional population of Ag-specific CD8(+) T cells from healthy individuals and vaccinated melanoma patients, respectively. Memory CD8(+) T cells stimulated with AT-SCT presented on MHC class I/II-null cells show reduced cytokine production, slower kinetics of TCR downregulation, and decreased cell death compared with native nonamer MHC class I single-chain trimer (SCT)-activated T cells. However, both ERK phosphorylation and cell cycle kinetics are identical in AT-SCT- and SCT-activated T cells. Probing of SCT and AT-SCT peptide-MHC complexes using fluorochrome-conjugated TCR multimers suggests that nonamer- and decamer-linked peptides may be anchored differently to the HLA-A2 peptide-binding groove. Our findings demonstrate that modified peptide-MHC structures, such as AT-SCT, can be engineered as T cell agonists to promote the growth and expansion of memory human CD8(+) T cells.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Antígeno HLA-A2/imunologia , Memória Imunológica/imunologia , Ativação Linfocitária/imunologia , Fragmentos de Peptídeos/imunologia , Apoptose/imunologia , Proliferação de Células , Citocinas/biossíntese , Citometria de Fluxo , Humanos , Proteínas Recombinantes de Fusão/imunologia
13.
Int J Antimicrob Agents ; 64(1): 107175, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38642812

RESUMO

OBJECTIVES: Colistin-induced nephrotoxicity prolongs hospitalisation and increases mortality. The study aimed to construct machine learning models to predict colistin-induced nephrotoxicity in patients with multidrug-resistant Gram-negative infection. METHODS: Patients receiving colistin from three hospitals in the Clinical Research Database were included. Data were divided into a derivation cohort (2011-2017) and a temporal validation cohort (2018-2020). Fifteen machine learning models were established by categorical boosting, light gradient boosting machine and random forest. Classifier performances were compared by the sensitivity, F1 score, Matthews correlation coefficient (MCC), area under the receiver operating characteristic (AUROC) curve, and area under the precision-recall curve (AUPRC). SHapley Additive exPlanations plots were drawn to understand feature importance and interactions. RESULTS: The study included 1392 patients, with 360 (36.4%) and 165 (40.9%) experiencing nephrotoxicity in the derivation and temporal validation cohorts, respectively. The categorical boosting with oversampling achieved the highest performance with a sensitivity of 0.860, an F1 score of 0.740, an MCC of 0.533, an AUROC curve of 0.823, and an AUPRC of 0.737. The feature importance demonstrated that the days of colistin use, cumulative dose, daily dose, latest C-reactive protein, and baseline haemoglobin were the most important risk factors, especially for vulnerable patients. A cutoff colistin dose of 4.0 mg/kg body weight/d was identified for patients at higher risk of nephrotoxicity. CONCLUSIONS: Machine learning techniques can be an early identification tool to predict colistin-induced nephrotoxicity. The observed interactions suggest a modification in dose adjustment guidelines. Future geographic and prospective validation studies are warranted to strengthen the real-world applicability.


Assuntos
Antibacterianos , Colistina , Farmacorresistência Bacteriana Múltipla , Registros Eletrônicos de Saúde , Infecções por Bactérias Gram-Negativas , Aprendizado de Máquina , Humanos , Colistina/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Idoso , Curva ROC , Adulto , Algoritmos , Estudos Retrospectivos
14.
Sci Transl Med ; 14(633): eabm1375, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35196021

RESUMO

Natural killer (NK) cells are innate lymphoid cells that eliminate cancer cells, produce cytokines, and are being investigated as a nascent cellular immunotherapy. Impaired NK cell function, expansion, and persistence remain key challenges for optimal clinical translation. One promising strategy to overcome these challenges is cytokine-induced memory-like (ML) differentiation, whereby NK cells acquire enhanced antitumor function after stimulation with interleukin-12 (IL-12), IL-15, and IL-18. Here, reduced-intensity conditioning (RIC) for HLA-haploidentical hematopoietic cell transplantation (HCT) was augmented with same-donor ML NK cells on day +7 and 3 weeks of N-803 (IL-15 superagonist) to treat patients with relapsed/refractory acute myeloid leukemia (AML) in a clinical trial (NCT02782546). In 15 patients, donor ML NK cells were well tolerated, and 87% of patients achieved a composite complete response at day +28, which corresponded with clearing high-risk mutations, including TP53 variants. NK cells were the major blood lymphocytes for 2 months after HCT with 1104-fold expansion (over 1 to 2 weeks). Phenotypic and transcriptional analyses identified donor ML NK cells as distinct from conventional NK cells and showed that ML NK cells persisted for over 2 months. ML NK cells expressed CD16, CD57, and high granzyme B and perforin, along with a unique transcription factor profile. ML NK cells differentiated in patients had enhanced ex vivo function compared to conventional NK cells from both patients and healthy donors. Overall, same-donor ML NK cell therapy with 3 weeks of N-803 support safely augmented RIC haplo-HCT for AML.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Imunidade Inata , Interleucina-15 , Células Matadoras Naturais , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia
15.
J Opt Soc Am A Opt Image Sci Vis ; 28(7): 1453-61, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21734745

RESUMO

A robust lensless optical data embedding system using both the computer-generated concealogram and the digital Fresnel hologram (DFH) is proposed. The concealogram and the DFH are cascaded as the input and filter planes, respectively. When the concealogram is illuminated by a plane wave, the hidden data can be extracted at the output plane without using any lenses. The longitudinal positions of the filter and the output planes, as well as the wavelength, can be used as the secret keys to enhance system security. Furthermore, the robustness of the proposed system against noise and distortion is also demonstrated.

16.
Hepatogastroenterology ; 58(105): 64-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21510288

RESUMO

BACKGROUND/AIMS: Stent deployment for the treatment of ERFs is typically performed under endoscopic guidance. Our aim was to evaluate self-expanding metallic stent placement under fluoroscopic guidance. METHODOLOGY: The records of six patients who underwent self-expanding metallic stent placement under fluoroscopic guidance for the treatment of ERFs were reviewed. Technical data of the procedures, complications, and associated morbidity were recorded. The main outcome measures were dysphagia score, KPS, and survival. RESULTS: Stents were successfully inserted in all 6 patients without complications, and all procedures were completed within 15 minutes. The mean dysphagia score was 4 +/- 0 before treatment and 1.2 +/- 0.8 one week after stent placement. The mean KPS increased significantly from 28.0 +/- 9.8 before stent placement to 58.3 +/- 16.0 one week after placement (p = 0.001). For the patients who had KPS < or =50 one week after the surgery, the survival period was relatively short (mean, 37 days). For the patients who had KPS > or =60 one week after the surgery, the mean survival period was 192 days. CONCLUSIONS: Self-expanding metallic stent placement can be performed safely and quickly under fluoroscopic guidance alone.


Assuntos
Neoplasias Esofágicas/terapia , Fluoroscopia , Fístula do Sistema Respiratório/terapia , Stents , Fístula Traqueoesofágica/terapia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/diagnóstico por imagem , Feminino , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Fístula do Sistema Respiratório/diagnóstico por imagem , Taxa de Sobrevida , Fístula Traqueoesofágica/diagnóstico por imagem , Resultado do Tratamento
17.
Sci Bull (Beijing) ; 66(7): 740-748, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36654448

RESUMO

The South China Sea (SCS) is the largest extensional basin in the western Pacific and was formed after rifting of the Euro-Asian continental margin. The nature of its underlying mantle remains enigmatic due to the lack of sampling of the seafloor's igneous crust. The International Ocean Discovery Program Expedition 349 cored seafloor basalts of the southwestern (Site U1433) and eastern (Site U1431) SCS sub-basins. The recovered basalt samples exhibit different source lithologies and geochemistries. The Mg isotopic compositions of seafloor basalts from these sites were investigated to elucidate the origin of this large-scale mantle inhomogeneity. Results indicate that the Site U1431 basalts have a mantle-like average δ26Mg value of -0.27‰ ± 0.06‰ (2SD; n = 10). Together with inhomogeneous Sr-Nd-Pb-Hf isotopic compositions, the Site U1433 basalts have an average δ26Mg value (-0.20‰ ± 0.06‰; 2SD; n = 8) higher than those of the Site U1431 basalts and normal mantle. Their heavier Mg isotopic compositions and low 206Pb/204Pb ratios (~17.7) indicate that the Site U1433 basalts were affected by the re-melting of detached continental-arc lithosphere in the sub-ridge mantle. The coupling of Mg and Sr-Nd isotopes provides robust evidence that the mantle-like δ26Mg values of the Site U1431 basalts resulted from mixing between detached continental arc lithosphere and the nearby Hainan plume, with respective supra- and sub-normal δ26Mg values. From the perspective of Mg isotope, the mantles of the southwestern and eastern sub-basins are compositionally inhomogeneous, with their mantle evolutionary histories being distinct.

18.
Front Chem ; 8: 594316, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363109

RESUMO

Clinopyroxene is a major host mineral for lithophile elements in the mantle lithosphere, and therefore, its origin is vital for constraints on mantle evolution and melt generation. In situ Sr isotopic measurement of clinopyroxene has been available since the recent development of laser ablation multicollector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) in the 2000s. Therefore, there is an increasing demand for natural clinopyroxene reference materials for Sr isotope microanalysis. In this contribution, we present six natural clinopyroxene reference materials from South Africa (JJG1424) and China (YY09-47, YY09-04, YY09-24, YY12-01, and YY12-02) for Sr isotope microanalysis. The Sr content of these clinopyroxenes ranges from 50 to 340 µg g-1, which covers most natural clinopyroxene compositions. Homogeneity of these potential reference materials were investigated and evaluated in detail over a 2-year period using 193-nm nanosecond and 257-nm femtosecond laser systems coupled to either a Neptune or Neptune Plus MC-ICP-MS. Additionally, the major and trace element of these clinopyroxenes were examined by electron probe microanalyzer (EPMA) as well as solution and laser ICP-MS. The in situ 87Sr/86Sr values obtained for the six natural clinopyroxene reference materials agree well with data obtained using the thermal ionization mass spectrometer (TIMS) method. The Sr isotopic stability and homogeneity of these clinopyroxenes make them potential reference materials for in situ Sr microanalysis to correct instrumental fractionation or as quality control materials for analytical sessions. The new Sr isotope data provided here might be beneficial for microbeam analysis in the geochemical community.

19.
Opt Express ; 17(16): 13700-10, 2009 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-19654778

RESUMO

A novel fast double-phase retrieval algorithm for lensless optical security systems based on the Fresnel domain is presented in this paper. Two phase-only masks are efficiently determined by using a modified Gerchberg-Saxton algorithm, in which two cascaded Fresnel transforms are replaced by one Fourier transform with compensations to reduce the consumed computations. Simulation results show that the proposed algorithm substantially speeds up the iterative process, while keeping the reconstructed image highly correlated with the original one.


Assuntos
Algoritmos , Segurança Computacional/instrumentação , Dispositivos Ópticos , Refratometria/instrumentação , Simulação por Computador , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Lentes , Luz , Modelos Teóricos , Espalhamento de Radiação , Medidas de Segurança
20.
Opt Lett ; 34(24): 3917-9, 2009 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-20016657

RESUMO

What we believe to be a new technique, based on a modified Gerchberg-Saxton algorithm (MGSA) and a phase modulation scheme in the Fresnel-transform domain, is proposed to reduce cross talks existing in multiple-image encryption and multiplexing. First, each plain image is encoded and multiplexed into a phase function by using the MGSA and a different wavelength/position parameter. Then all the created phase functions are phase modulated to result in different shift amounts of the reconstruction images before being combined together into a single phase-only function. Simulation results show that the cross talks between multiplexed images have been significantly reduced, compared with prior methods [Opt. Lett.30, 1306 (2005); J. Opt. A8, 391 (2006)], thus presenting high promise in increasing the multiplexing capacity and encrypting grayscale and color images.

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